I don't really see any reason why you couldn't just do a setwise comparison and check which of the extraversion increasing variants (or combinations of variants if epistatic effects dominate) increase the trait without increasing conformity to social desirability.

In fact if you just select for disagreeableness as well that might just fix the problem.

The key distinction is that IQ demonstrates a robust common pathway structure - different cognitive tests correlate with each other because they're all tapping into a genuine underlying cognitive ability. In contrast, personality measures often fail common pathway tests, suggesting that the correlations between different personality indicators might arise from multiple distinct sources rather than a single underlying trait. This makes genetic selection for personality traits fundamentally different from selecting for IQ - not just in terms of optimal selection strength, but in terms of whether we can meaningfully select for the intended trait at all.

There is such a thing as a "general factor of personality". I'm not sure how you can say that the thing IQ is measuring is real while the general factor of personality isn't.

Sure big 5 aren't the end-all be-all of personality but they're decent and there's no reason you couldn't invent a more robust measure for the purpose of selection.

I think we would probably want to select much less hard on personality than on IQ. For virtually any one of the big five personality traits there is obviously a downside to becoming too extreme. For IQ that's not obviously the case.

Paper 1 is pretty interesting and is related to one of the methods of brain delivery I've looked at before.

I'm not sure we really want to have a lot of T cells floating around inside the central nervous system, but a friend of mine who spent a few days looking into this earlier this year thought we might be able to repurpose the same tech with synthetic circuits to use microglia cells in the brain to do delivery.

Microglia (and to a lesser extent oligodendrocytes and astrocytes) naturally migrate around the brain. If you could get them to deliver RNA, DNA or RNP payloads to cells when they encounter a tissue-specific cell surface receptor, that might actually solve the brain delivery issue better than any other method.

This would take a lot of work to develop, but if you managed to get it working you could potentially continuously dose a patient's brain with an arbitrary protein for an indefinite time period. That could be pretty damn valuable.

Alternatively you might be able to use a conditionally activated system like Tet-On to temporarily turn on expression of gene editors or gene editor RNA for some time period to do editing.

Yes. Once this tech works you can use it for basically anything so long as you can make enough edits and the genes involved are known.

So we really don’t need to make any special considerations for memory.

We will be hiring fairly soon. Reach out to me genesmithlesswrong@gmail.com

Good question! What’s the name of the skin condition you have?

Yeah I pretty much agree with this assessment. I think you could probably get to 80% with 100 million and ten years and maybe 50% with 30 million and 7 years. Perhaps I'm optimistic, but right now the entire field is bottlenecked by the need for $4 million to do primate testing.

Aspen dental is a franchise based venture capital funded organization that already does this.

This is interesting, thanks for sharing.

I asked my friend about your other concerns regarding enshittification of the dental industry. If you're interested, this was their response:

Patients tend to do better with DSOs. There’s a number of reasons:

1. The first is doctor supervision—when doctors have their own offices, no one checks their work or holds them accountable. In a corporate setting, there is typically a clinical director that the doctors will report to.
2. The second issue is that the worst case is actually the doctor being the owner—that’s when they have the strongest financial incentive to do bullshit. The more the doctor is removed from being the owner, the less I think their judgement is influenced.

Now in nearly all DSOs and private practices, revenue is the chief KPI for doctors. So the pressure is there still to a degree.

With us, revenue is not a KPI—we don’t ever tell the doctors how much they produce And so we remove the financial biasing of their diagnosis and treatment.

But we are unique in this—definitely an outlier in how much we are trying to have the doctors be unbiased by the finances.

What’s also ironic about some of the replies is that our lobby goals are to actually get real regulation put into place so patients are protected from doctors doing whatever to maximize revenue But these somewhat personal ideals and goals being acted out—that do run counter to the pure capitalist logic

@towards_keeperhood yes this is correct. Most research seems to show ~80% of effects are additive.

Genes are actually simpler than most people tend to think

You’re ignoring several facts:

1. A significant fraction of cells turn over frequently in adults so the number of divisions for those cell types is far, far higher than 45 divisions. Those cell divisions CAN cause cancer, it a single extra cell division is going to have negligible impact on risk.
2. There’s an enzyme called telomerase which can extend telomeres. It’s active in embryos. So this isn’t really a concern.